Overview
Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2025-12-31
2025-12-31
Target enrollment:
0
0
Participant gender:
All
All
Summary
Background: Immunotherapy is a powerful tool in the fight against cancer. It uses the body s own immune system to fight the cancer. Unfortunately, cancer cells can find ways to escape from destruction by the body s immune system, even when immunotherapy is used. Natural killer (NK) cells are an important part of the body s immune system and can help fight cancer. In combination with immunotherapy, researchers are using engineered NK cells that recognize and kill cancer cells trying to escape destruction by the immune system. Objective: To test the effectiveness of irradiated PD-L1 CAR-NK cells, combined with pembrolizumab and N-803, in people with advanced forms of gastric or head and neck cancer. Eligibility: Adults ages 18 and older with advanced gastric or head and neck cancer who have already had standard cancer treatment. Design: Participants will be screened with a medical history and physical exam. Their symptoms and ability to do normal activities will be assessed. They will have blood and urine tests. They will have imaging scans of the chest, abdomen, and pelvis. Participants will get PD-L1 CAR-NK cells by intravenous (IV) infusion. They will get the cells once a week for 6 weeks. Then they will get the cells once every 2 weeks. Before each infusion, an IV catheter will be placed in a large arm vein for infusion of these treatments. Participants will get pembrolizumab by IV every 6 weeks. They will get N-803 under the skin every 4 weeks. Participants will get the study drugs for up to 2 years. They will have study visits every 1-2 weeks during treatment. They will have a safety visit 28 days after treatment ends. After treatment ends, participants will be contacted for follow-up every 2 months for a year. Then they will be contacted every 6 months. They will have tumor scans every 6-12 weeks until their cancer gets worse.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
National Cancer Institute (NCI)Treatments:
Pembrolizumab
Criteria
- INCLUSION CRITERIA:- Gastric/GEJ cancer Cohort:
- Participants must have metastatic or unresectable locally advanced Gastric/GEJ
cancer that has been histologically confirmed.
- Participants must have measurable disease by RECISTv1.1.
- Participants must have received or been ineligible to receive first line systemic
chemotherapy for Gastric/GEJ cancer. Participants with HER2 positive disease must
have received HER2-targeted therapy.
- Head and neck squamous cell carcinoma Cohort
- Participants must have metastatic or unresectable locally advanced HNSCC that has
been histologically confirmed.
- Participants must have measurable disease by RECISTv1.1.
- Participants must have received or been ineligible to receive first-line systemic
chemotherapy and must have received systemic anti-PD-1 therapy (in the first-line
or subsequent-line setting).
- Age >=18 years. Because no dosing or adverse event data are currently available on the
use of this investigation combination therapy in participants <18 years of age,
children are excluded from this study, but will be eligible for future pediatric
trials.
- ECOG performance status <2
- Participants must have adequate organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of
normal
- creatinine Creatinine within 1.5X upper limit of normal institutional limits
- Participants with treated brain metastases are eligible if follow-up brain imaging
after central nervous system (CNS)-directed therapy shows no evidence of progression.
- Participants with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate CNS specific treatment is not required and is unlikely to be required during
the first 7 weeks of therapy.
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For participants with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load.
- Participants on therapeutic anticoagulation with warfarin must have an international
normalized ratio (INR) that is within target range for their condition at the time of
enrollment.
- The effects of PD-L1 t-haNKs with N-803 and pembrolizumab on the developing human
fetus are unknown. For this reason and because these investigational agents
teratogenicity is unknown, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry for the duration of study participation and for at least 4 months after last
dose of study drug pembrolizumab.
-Ability of subject to understand and the willingness to sign a written informed consent
document.
EXCLUSION CRITERIA:
- Participants who are receiving any other investigational agents or concurrent
anticancer treatment. Palliative radiotherapy is allowed.
- Participants with concurrent use of systemic steroids (within 10 days of enrollment),
except for physiologic doses of systemic steroid replacement or local (topical, nasal,
intraarticular or inhaled) steroid use.
- Participants with active systemic autoimmune disease (e.g., lupus erythematosus,
rheumatoid arthritis, Addison s disease, autoimmune disease associated with lymphoma,
inflammatory bowel disease). Participants with autoimmune endocrine disorders
controlled with medical management (e.g. thyroid disorders, type 1 diabetes, or
adrenal insufficiency) will not be excluded
- Participants with a history of grade 3 or higher immune-related adverse events
attributed to pembrolizumab or other anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
This exclusion does not apply to participants with permanent endocrine insufficiencies
(e.g. adrenal insufficiency or hypothyroidism) under satisfactory medical management.
Additionally, participants with grade 2 adverse events attributed to these classes of
agents will be excluded with the exception of rash, transient hyperthyroidism,
transient liver enzyme abnormalities or other transient events that resolved without
steroids or immunomodulatory agents.
- HIV or HBV infection due to unknown effect of PD-L1 targeting via a CAR or N-803 in
these chronic viral infections.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris,
uncontrolled serious cardiac arrhythmia, clinically significant coagulopathy or
psychiatric illness/social situations that would limit compliance with study
requirements.
- Pregnant women are excluded from this study because PD-L1 targeting via a CAR has
unknown potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the
mother with PD-L1 targeting via a CAR and N-803, breastfeeding should be discontinued if
the mother is treated on this study for the duration of study participation and for at
least 4 months after last dose of any study drug.